Development of a Novel Cancer Pain Therapeutic Pain due to cancer is one of the great fears, at times greater than even death, in the progression of the disease. Numerous studies have shown the preponderance of pain in terminal cases. But even worse, many times this pain is refractory to the last stand treatment: opioids. We engineered the recombinant targeted toxin, substance P-saporin (SP-SAP) and showed selective toxicity to NK1R- bearing neurons. A single intrathecal (IT) infusion of SP-SAP alleviated pathologic pain perception without affecting other sensory signal pathways in rats and dogs. In pre-IND discussions with the Food and Drug Administration (FDA), SP-SAP was considered to be an important new approach for the treatment of cancer pain in patients refractory to opioids. Specific Aims for this proposal are designed to respond to requests from the FDA, prepare for an Investigative New Drug Application and complete a Phase 1/2 clinical trial in cancer patients with pain that is refractory to opioids. A top level team of groups with the expertise to complete these Specific Aims has been assembled. The studies proposed here will provide critical information leading to pivotal clinical trials and eventual commercialization of a completely innovative therapy for cancer pain. PUBLIC HEALTH RELEVANCE: Development of a Novel Cancer Pain Therapeutic Pain due to cancer is one of the great fears, at times greater than even death, in the progression of the disease. The studies proposed here will provide critical information leading to pivotal clinical trials and eventual commercialization of a completely innovative therapy for cancer pain.